Processing difficulties and instability of carbohydrate microneedle arrays.
Processing difficulties and instability of carbohydrate microneedle arrays.
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DOI：
10.1080/03639040902882280
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发表时间：
2009-10
影响因子：
3.4
通讯作者：
Woolfson AD
中科院分区：
文献类型：
--
作者：
Donnelly RF;Morrow DI;Singh TR;Migalska K;McCarron PA;O'Mahony C;Woolfson AD
许多报道已经表明，目前与用于透皮药物递送的微针（MN）阵列的使用相关的许多问题可以通过使用通过模制碳水化合物材料的热熔体制备的载药MN阵列来解决。在这项研究中，我们探讨了从半乳糖制备的MN阵列的加工，处理和储存，以期临床应用。半乳糖需要高的加工温度（160°C），并且熔化的半乳糖难以加工。模型药物5-氨基乙酰丙酸（ALA）和牛血清白蛋白在加工过程中发生了大量损失。虽然相对较小的力导致MN高度显着降低时，施加到铝块，这是没有观察到在他们相对容易插入到热剥离表皮。使用ALA-加载的MN阵列的药物释放实验显示，小于0.05%的总载药量通过模型硅树脂膜释放。类似地，当半乳糖阵列与水性载体组合时，仅递送少量ALA（约0.13%）和不可检测量的牛血清白蛋白。释放研究后对膜的显微镜检查显示，在膜中未观察到孔，表明部分溶解的半乳糖密封了MN诱导的孔，从而限制了药物递送。实际上，对切除的猪皮的深度渗透研究揭示，与对照相比，使用半乳糖MN阵列的ALA递送没有显著增加（P值< 0.05）。半乳糖MNs在环境相对湿度下不稳定，并成为粘合剂。本研究中遇到的加工困难和不稳定性可能会妨碍碳水化合物MN的成功临床应用。这项研究的结果是特别重要的那些在制药行业参与的设计和制定的经皮给药系统的基础上溶解MN阵列。希望我们已经明确说明了基于碳水化合物的溶解MN的加工和储存中固有的困难，并且工业中的那些人现在将遵循替代方法。
A number of reports have suggested that many of the problems currently associated with the use of microneedle (MN) arrays for transdermal drug delivery could be addressed by using drug-loaded MN arrays prepared by moulding hot melts of carbohydrate materials. In this study, we explored the processing, handling, and storage of MN arrays prepared from galactose with a view to clinical application. Galactose required a high processing temperature (160°C), and molten galactose was difficult to work with. Substantial losses of the model drugs 5-aminolevulinic acid (ALA) and bovine serum albumin were incurred during processing. While relatively small forces caused significant reductions in MN height when applied to an aluminium block, this was not observed during their relatively facile insertion into heat-stripped epidermis. Drug release experiments using ALA-loaded MN arrays revealed that less than 0.05% of the total drug loading was released across a model silicone membrane. Similarly, only low amounts of ALA (approximately 0.13%) and undetectable amounts of bovine serum albumin were delivered when galactose arrays were combined with aqueous vehicles. Microscopic inspection of the membrane following release studies revealed that no holes could be observed in the membrane, indicating that the partially dissolved galactose sealed the MN-induced holes, thus limiting drug delivery. Indeed, depth penetration studies into excised porcine skin revealed that there was no significant increase in ALA delivery using galactose MN arrays, compared to control (P value < 0.05). Galactose MNs were unstable at ambient relative humidities and became adhesive. The processing difficulties and instability encountered in this study are likely to preclude successful clinical application of carbohydrate MNs. The findings of this study are of particular importance to those in the pharmaceutical industry involved in the design and formulation of transdermal drug delivery systems based on dissolving MN arrays. It is hoped that we have illustrated conclusively the difficulties inherent in the processing and storage of carbohydrate-based dissolving MNs and that those in the industry will now follow alternative approaches.
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DOI：
10.1073/pnas.2331316100
发表时间：
2003-11-25
影响因子：
11.1
作者：
McAllister, DV;Wang, PM;Prausnitz, MR
通讯作者：
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影响因子：
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DOI：
10.1016/j.jphotobiol.2005.08.007
发表时间：
2006-01-02
影响因子：
5.4
作者：
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通讯作者：
Woolfson, AD
影响因子：
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